title: Effects of raloxifene on the production of cytokines in stimulated whole blood in ex vivo and in vitro studies.
abstract: OBJECTIVE
  The aims of this study were to determine the effects of raloxifene therapy on production of cytokines and in vitro effects of raloxifene on production of cytokines by whole blood cultures.
  
  
  METHODS
  We obtained samples of peripheral blood from 6 postmenopausal women with osteopenia at baseline and after 3 and 6 months of raloxifene therapy and 10 postmenopausal women who did not receive raloxifene therapy. Whole blood from raloxifene-treated women was stimulated with lipopolysaccharide (LPS) or phytohemeagglutinin (PHA). Whole blood from postmenopausal women who were not treated with raloxifene was preincubated with raloxifene at concentrations of 10(-10)-10(-7) M and then stimulated with LPS or PHA. Concentrations of IL-1β, IL-4, IL-6, IL-12p40, IL-12p70, TNF-α and IFN-γ in the supernatant were measured by respective ELISAs.
  
  
  RESULTS
  In ex vivo cultures, raloxifene therapy inhibited LPS-stimulated production of IL-1β, IL-6, IL-12p40, IL-12p70 and TNF-α, but not PHA-stimulated production of IL-4 and IFN-γ. In in vitro cultures, raloxifene at a concentration (10(-9) M) inhibited LPS-stimulated production of IL-1β, IL-6 and IL-12p40 and PHA-stimulated production of IFN-γ.
  
  
  CONCLUSIONS
  Raloxifene therapy decreases the production of IL-1β, IL-6, IL-12 and TNF-α but not that of IL-4 and IFN-γ, suggesting that modulation of cytokines could play a role in the mechanisms of the osteoprotective effect of raloxifene.
authors.affiliation: Department of Obstetrics and Gynecology, Tokushima Prefectural Central Hospital, Tokushima, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kasai
authors.forename: Masahiko
authors.initials: M
authors.lastname: Maegawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Masaharu
authors.initials: M
authors.lastname: Kamada
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yasui
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Uemura
authors.forename: Ayako
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Masayo
authors.initials: M
authors.lastname: Kaneyama
authors.forename: Anna
authors.initials: A
authors.lastname: Tani
authors.forename: Sumika
authors.initials: S
authors.lastname: Matsui
authors.forename: Akira
authors.initials: A
authors.lastname: Kuwahara
authors.forename: Toshiya
authors.initials: T
authors.lastname: Matsuzaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Furumoto
authors.forename: Minoru
authors.initials: M
authors.lastname: Irahara
mesh_terms: D000368:Aged; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001851:Bone Diseases, Metabolic / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008593:Menopause / Q000097:blood / Q000276:immunology; D008875:Middle Aged; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D050071:Bone Density Conservation Agents; D016207:Cytokines; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride